Clinically Relevant Postoperative Pancreatic Fistula Research Articles

Risk factors and nomogram of clinically relevant pancreatic fistula after pancreaticoduodenectomy for periampullary cancer: A prospective multicenter cohort study

Abstract Background Clinically relevant postoperative pancreatic fistula (CRPF) is considered the most dangerous morbidity associated with pancreaticoduodenectomy (PD). The purpose of this study is to evaluate the risk factors and to construct a predicted model for CRPF after PD. Material and Methods Consecutive patients who underwent pancreaticoduodenectomy between August 2021 and October 2023 at Cho Ray Hospital and University Medical Center were included in a multicenter cohort research. Multivariate logistic regression analyses was used to identify the risk factors of CRPF, and a nomogram was built based on these factors. The value of the nomogram in predicting CRPF was evaluated using the area under the receiver operating characteristic (ROC) curve. Results There were 183 eligible patients in this study (mean age: 57.5 ± 12.6 years; 101 males), and the prevalence of CRPF was 13,7% overall. Multivariate analyses showed that, four risk factors related to CRPF, including preoperative serum albumin <3.5 g/dl, body mass index (BMI) ≥ 25 kg/m2, soft texture of the pancreas and estimated blood loss ≥400 ml were prognostic factors for CRPF (p < 0.05). We built a nomogram based on four variables to predict CRPF, and the area under the ROC curve for this nomogram was 0.855 (95% CI: 0,768 – 0,933). Conclusions Nomogram developed from four risk factors shows good performance to predict CRPF after PD. The clinical findings of this study will help surgeons identify perioperative risk factors for high-risk patients with pancreatic fistula who should be managed differently from other patients. Clinical Trial Registry number: ClinicalTrials.gov NCT05017207. Statement of Significance We successfully developed a nomogram to predict the risk of pancreatic fistula using four perioperative factors. By incorporating these risk factors into clinical practice, surgeons can develop appropriate treatment plans and interventions for high-risk patient populations, potentially reducing the morbidity associated with CRPF.

Efficacy of pancreaticojejunostomy of the pancreatic stump during distal or central pancreatectomy.

A stapler is usually used for transection and closure of the pancreas in distal pancreatectomy (DP) or central pancreatectomy (CP). When the pancreas is transected to the right of the portal vein, it is difficult to use a stapler and clinically relevant postoperative pancreatic fistula (CR-POPF) frequently occurs. We report on the efficacy of pancreaticojejunostomy (PJ) of the pancreatic stump for patients in whom stapler use is difficult. Patients who underwent DP or CP were enrolled in this study. The pancreas was usually transected by a stapler, and ultrasonic coagulating shears (UCS) were used depending on the tumor situation. When using UCS, hand-sewn closure or PJ was performed for the pancreatic stump. The relationship between clinicopathological factors and the methods of pancreatic transection and closure were investigated. In total, 164 patients underwent DP or CP, and the pancreas was transected with a stapler in 150 patients and UCS in 14 patients. The rate of CR-POPF was higher and the postoperative hospital stay was longer in the UCS group than in the stapler group. PJ of the pancreatic stump, which was performed for 7 patients, did not worsen intraoperative factors. CR-POPF was not seen in these 7 patients, which was significantly less than that with hand-sewn closure. PJ of the pancreatic stump during DP or CP reduces CR-POPF compared with hand-sewn closure and may be useful especially when the pancreas is transected to the right of the portal vein.

Does perioperative hydrocortisone or indomethacin improve pancreatoduodenectomy outcomes? A triple arm, randomized placebo-controlled trial.

This trial evaluated whether anti-inflammatory agents hydrocortisone (H) and indomethacin (I) could reduce major complications after pancreatoduodenectomy (PD). Between June 2018 and June 2020, 105 patients undergoing PD with > 40% of acini on the intraoperative frozen section were randomized into three groups (35 patients per group): 1) intravenous H 100 mg 8 hourly, 2) rectal I suppository 100 mg 12 hourly, and 3) placebo (P) from postoperative day (POD) 0-2. Participants, investigators, and outcome assessors were blinded. The primary outcome was major complications (Clavien-Dindo grades 3-5). Secondary outcomes were overall complications (Clavien-Dindo grades 1-5), Clinically relevant postoperative pancreatic fistula (CR-POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), surgical site infections (SSI), length of stay, POD-3 serum amylase, readmission rate, and mortality. Major complications were comparable (8.6%, 5.7%, and 8.6% in groups H, I, and P, respectively). However, overall complications were significantly lower in group H than in group P (45.7% vs. 80.0%, p = 0.006). CR-POPF (14.3% vs. 25.7%, p = 0.371), PPH (8.6% vs. 14.3%, p = 0.710), DGE (8.6% vs. 22.9%, p = 0.188), and SSI (14.3% vs. 25.7%, p = 0.371) were comparable between groups H and P. Major complications and overall complications in group I were 5.7% and 60.0%, respectively, which were comparable to those in groups P and H. CR-POPF rates in groups H, I, and P were 14.3%, 17.1%, and 25.7%, respectively, which was comparable. H and I did not decrease major complications in PD.

Preoperative ultrasound radiomics for predicting clinically relevant postoperative pancreatic fistula after pancreatectomy.

To evaluate the efficacy of the radiomics model based on preoperative B-mode ultrasound (BMUS) and shear wave elastography (SWE) for predicting the occurrence of clinically relevant-postoperative pancreatic fistula (CR-POPF). Patients who were scheduled to undergo pancreatectomy were prospectively enrolled and received ultrasound assessment within one week before surgery. The risk factors of POPF (grades B and grades C) were analyzed. Preoperative BMUS images, SWE values of pancreatic lesions and surrounding parenchyma were used to build preoperative prediction radiomics models. Radiomic signatures were extracted and constructed using a minimal Redundancy Maximal Relevance (mRMR) algorithm and an L1 penalized logistic regression. A combined model was built using multivariate regression which incorporated radiomics signatures and clinical data. From January 2020 to November 2021, a total of 147 patients (85 distal pancreatectomies and 62 pancreaticoduodenectomies) were enrolled. During the three-week follow-up after pancreatectomy, the incidence rates of grade B/C POPF were 28.6% (42/147). Radiomic signatures constructed from BMUS of pancreas parenchymal regions (panRS) achieved an area under the receiver operating characteristic curve (AUC) of 0.75, accuracy of 68.7%, sensitivity of 85.7 %, and specificity of 61.9 % in preoperative noninvasive prediction of CR-POPF. The AUC of the radiomics model increased to 0.81 when panRS was used for the prediction of CR-POPF after pancreaticoduodenectomy. Radiomics model based on ultrasound images was potentially useful for predicting CR-POPF. Patients with high-risk factors should be closely monitored when postoperation.

Stent placement for the prevention of clinically-relevant postoperative pancreatic fistula following pancreaticojejunostomy: A systematic review and meta-analysis

ObjectivesThere remains a lack of consensus regarding the benefits of stent placement following pancreaticojejunostomy in terms of clinically relevant postoperative pancreatic fistulas (CR-POPFs). This study was aimed at analyzing the effects of stent placement, stent technique (internal and external), stent size, and dilation of the main pancreatic duct on CR-POPFs. MethodsOur study comprised a systematic review and meta-analysis of randomized controlled trials involving patients undergoing pancreaticojejunostomy. The primary outcome was defined as the incidence of CR-POPFs. Additionally, subgroup analyses were conducted, and pooled analyses were performed to provide comparative references. ResultsTwelve randomized controlled trials, including a total of 1117 patients, were included. Compared with no stent placement, stenting did not exhibit a significant association with reduced CR-POPF incidence (odds ratio [OR] ​= ​0.60, 95% CI: 0.34–1.04, P ​= ​0.07). Subgroup analysis revealed that only external stents, and not internal stents, were significantly associated with a reduced CR-POPF incidence compared with no stent placement (OR ​= ​0.53, 95% CI: 0.28–0.99, P ​= ​0.05 vs. OR ​= ​0.92, 95% CI: 0.28–3.05, P ​= ​0.89). Furthermore, stent placement in patients with a main pancreatic duct diameter of ≤3 ​mm, and not in those with a main pancreatic duct diameter of >3 ​mm, was associated with a significantly reduced CR-POPF incidence compared with no stent placement (OR ​= ​0.24, 95% CI: 0.07–0.78, P ​= ​0.02 vs. OR ​= ​1.58, 95% CI: 0.41–6.06, P ​= ​0.50). ConclusionsThe findings suggest a potential role for external stent placement in the prevention of CR-POPFs after pancreaticojejunostomy, particularly in patients with undilated pancreatic ducts. The reliability of our findings is constrained by the limited number of studies included. Prospero registration numberCRD42022380103.

Optimal cutoff values of drain amylase for predicting pancreatic fistula are different between open and laparoscopic distal pancreatectomy.

Drainage fluid amylase (DFA) is useful for predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP). However, difference in optimal cutoff value of DFA for predicting CR-POPF between open DP (ODP) and laparoscopic DP (LDP) has not been investigated. This study aimed to identify the optimal cutoff values of DFA for predicting CR-POPF after ODP and LDP. Data for 294 patients (ODP, n=127; LDP, n=167) undergoing DP at Kobe University Hospital between 2010 and 2021 were reviewed. Propensity score matching was performed to minimize treatment selection bias. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff values of DFA for predicting CR-POPF for ODP and LDP. Logistic regression analysis for CR-POPF was performed to investigate the diagnostic value of DFA on postoperative day (POD) three with identified cutoff value. In the matched cohort, CR-POPF rates were 24.7% and 7.9% after ODP and LDP, respectively. DFA on POD one was significantly lower after ODP than after LDP (2263U/L vs 4243U/L, p<0.001), while the difference was not significant on POD three (543U/L vs 1221U/L, p=0.171). ROC analysis revealed that the optimal cutoff value of DFA on POD one and three for predicting CR-POPF were different between ODP and LDP (ODP, 3697U/L on POD one, 1114U/L on POD three; LDP, 10564U/L on POD one, 6020U/L on POD three). Multivariate analysis showed that DFA on POD three with identified cutoff value was the independent predictor for CR-POPF both for ODP and LDP. DFA on POD three is an independent predictor for CR-POPF after both ODP and LDP. However, the optimal cutoff value for it is significantly higher after LDP than after ODP. Optimal threshold of DFA for drain removal may be different between ODP and LDP.

A combined score for predicting clinically relevant postoperative pancreatic fistula based on inflammatory parameters and drainage fluid culture results on postoperative day 3.

Clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatic resection can lead to severe postoperative complications. POPF is defined based on postoperative day (POD) 3 drainage fluid amylase level. POPF correlates with inflammatory parameters as well as drainage fluid bacterial infection. However, a standardized model based on these factors for predicting CR-POPF remains elusive. We aimed to identify inflammatory parameter- and drainage fluid culture-related risk factors for CR-POPF on POD 3 after pancreatoduodenectomy (PD) and distal pancreatectomy (DP). Data from 351 patients who underwent PD or DP between 2013 and 2022 at a single institution were retrospectively analyzed. Risk factors for CR-POPF were investigated using multivariate analyses, and a prediction model combining the risk factors for CR-POPF was developed. Of the 351 patients, 254 and 97 underwent PD and DP, respectively. Multivariate analyses revealed that drainage fluid amylase level ≥722 IU/L, culture positivity, as well as neutrophil count ≥5473/mm3 on POD 3 were independent risk factors for CR-POPF in PD group. Similarly, drainage fluid, amylase level ≥500 IU/L, and culture positivity on POD 3 as well as pancreatic thickness ≥11.1mm were independent risk factors in the DP group. The model for predicting CR-POPF achieved the maximum overall accuracy rate when the number of risk factors was ≥2 in both the PD and DP groups. Inflammatory parameters on POD 3 significantly influence the risk of CR-POPF onset after pancreatectomy. The combined models based on these values can accurately predict the risk of CR-POPF after pancreatectomy.

Revealing the role of early peripancreatic bacterial contamination and Enterococcus faecalis in pancreatic fistula development after pancreaticoduodenectomy: Implications for useful antibiotic prophylaxis–An observational cohort study

BackgroundPeripancreatic bacterial contamination (PBC) is a critical factor contributing to the development of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). Controlling pathogenic bacteria is essential in preventing CR-POPF; however, the precise relationship between specific bacteria and CR-POPF remains unclear. This study aimed to investigate the relationship between PBC and CR-POPF after PD, with a focus on identifying potentially causative bacteria. MethodsThis prospective observational study enrolled 370 patients who underwent PD. Microbial cultures were routinely collected from peripancreatic drain fluid on postoperative days (PODs) 1, 3, and 6. Predictive factors for CR-POPF and the bacteria involved in PBC were investigated. ResultsCR-POPF occurred in 86 (23.2%) patients. In multivariate analysis, PBC on POD1 (Odds ratio [OR] = 3.59; P = 0.005) was one of the main independent predictive factors for CR-POPF, while prophylactic use of antibiotics other than piperacillin/tazobactam independently influenced PBC on POD1 (OR = 2.95; P = 0.010). Notably, Enterococcus spp., particularly Enterococcus faecalis, were significantly isolated from PBC in patients with CR-POPF compared to those without CR-POPF on PODs 1 and 3 (P < 0.001), and they displayed high resistance to all cephalosporins. ConclusionsEarly PBC plays a pivotal role in the development of CR-POPF following PD. Prophylactic antibiotic administration, specifically targeting Enterococcus faecalis, may effectively mitigate early PBC and subsequently reduce the risk of CR-POPF. This research sheds light on the importance of bacterial control strategies in preventing CR-POPF after PD.

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

Machine learning models and nomogram based on clinical, laboratory profiles and skeletal muscle index to predict pancreatic fistula after pancreatoduodenectomy.

Postoperative pancreatic fistula (POPF) is a perilous complication that may arise subsequent to pancreaticoduodenectomy (PD). In recent times, there has been an escalating interest in employing machine learning (ML) techniques to aid in treatment decision-making. The purpose of this research is to assess the effectiveness of ML in comparison to conventional models, while also conducting an initial evaluation of the predictive capability of skeletal muscle index (SMI) concerning POPF. This retrospective observational study was carried out at The First Affiliated Hospital of Wenzhou Medical University from January 2012 to January 2021, encompassing data from 269 patients who underwent PD. After identifying independent factors associated with the condition, a logistic regression model was employed to construct a nomogram, alongside the establishment of five ML models. To assess their effectiveness, the best-performing ML model and nomogram were evaluated on a separate test group comprising 77 additional patients. The evaluation involved comparing the area under the curve (AUC) and Brier score. Among the 269 patients studied, the incidence of POPF was found to be 56.9%, with 106 patients (69.3%) experiencing clinically-relevant POPF. We identified six independent factors associated with POPF, including body mass index (BMI), SMI, pancreatic duct dilatation, tumor size, triglyceride levels, and the ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT) on the first postoperative day. When evaluated on the test set, the Gaussian Naive Bayes (GNB) model, which was the best-performing ML model, achieved an AUC of 0.824 and a Brier score of 0.175. The corresponding performance indicators for the nomogram were 0.844 for AUC and 0.165 for the Brier score. This study found that there is minimal difference between ML and the nomogram based on logistic regression in predicting POPF. Additionally, SMI shows promise as a potential and practical tool for assessing the risk of POPF.

Association of Postoperative Hyperamylasemia With Clinically Relevant Postoperative Pancreatic Fistula in Pancreatoduodenectomy.

Background In this study, we aimed to determine the association between postoperative hyperamylasemia (POH) and clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). Methodology A prospective observational study of 140 consecutive PDs between March 2020 and March 2022 was conducted. POH was defined as an elevation in serum pancreatic amylase levels above the institutional upper limit of normal on postoperative day (POD) 1 (>100 U/L). CR-POPF was defined as the International Study Group of Pancreatic Surgery Grade B or C POPF. The primary outcome was the rate of CR-POPF in the study population. The trial was prospectively registered with Clinicaltrials.gov (NCT04514198). Results In our study, 93 (66.42%) patients had POH (serum amylase >100 U/L). CR-POPF developed in 48 (34.28%) patients: 40 type B and 8 type C. CR-POPF rate was 43.01% (40/93) in patients with POH compared to 17.02% (8/47) in patients without POH (p = 0.0022). Patients with POH had a mean serum amylase of 422.7 ± 358.21 U/L on POD1 compared to 47.2 ± 20.19 U/L in those without POH (p < 0.001). Serum amylase >100 U/L on POD1 was strongly associated with developing CR-POPF (odds ratio = 3.71; 95% confidence interval = 1.31-10.37) on logistic regression, with a sensitivity and specificity of 83.3% and 42.4%, respectively. Blood loss >350 mL, pancreatic duct size <3 mm, and elevated POD1 serum amylase >100 U/L were predictive of CR-POPF on multivariate analysis (p < 0.001). Conclusions An elevated serum amylase on POD1 may help identify patients at risk for developing POPF following PD.

Independent external validation and comparison of existing pancreatic fistula risk scores after laparoscopic pancreaticoduodenectomy with Bing’s pancreaticojejunostomy

The fistula risk score (FRS) is the widely acknowledged prediction model for clinically relevant postoperative pancreatic fistula (CR-POPF). In addition, the alternative FRS (a-FRS) and updated alternative FRS (ua-FRS) have been developed. This study performed external validation and comparison of these 3 models in patients who underwent laparoscopic pancreaticoduodenectomy (LPD) with Bing's pancreaticojejunostomy. The FRS total points and predictive probabilities of a-FRS and ua-FRS were retrospectively calculated using patient data from a completed randomized controlled trial. Postoperative pancreatic fistula (POPF) and CR-POPF were defined according to the 2016 International Study Group of Pancreatic Surgery criteria. The correlations of the 4 risk items of the FRS model with CR-POPF and POPF were analyzed and represented using the Cramer V coefficient. The performance of the 3 models was measured using the area under the curve (AUC) and calibration plot and compared using the DeLong test. This study enrolled 200 patients. Pancreatic texture and pathology had discrimination for CR-POPF (Cramer V coefficient: 0.180 vs 0.167, respectively). Pancreatic duct diameter, pancreatic texture, and pathology had discrimination for POPF (Cramer V coefficient: 0.357 vs 0.322 vs 0.257, respectively). Only the calibration of a-FRS predicting CR-POPF was good. The differences among the AUC values of the FRS, a-FRS, and ua-FRS were not statistically significant (CR-POPF: 0.687 vs 0.701 vs 0.710, respectively; POPF: 0.733 vs 0.741 vs 0.750, respectively). After recalibrating, the ua-FRS got sufficient calibration, and the AUC was 0.713 for predicting CR-POPF. For LPD cases with Bing's pancreaticojejunostomy, the 3 models predicted POPF with better discrimination than predicting CR-POPF. The recalibrated ua-FRS had sufficient discrimination and calibration for predicting CR-POPF.

No Drain, No Problem: Serum-Based Marker Prediction of Clinically Relevant Postoperative Pancreatic Fistula.

Postoperative day (POD) 1 drain amylase concentration (DAC) is considered the most accurate predictor for the development of a clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). Recent studies have associated drain placement with negative postoperative outcomes. This study aims to evaluate multiple biochemical markers and their associations with CR-POPF development in order to identify a reliable, non-drain dependent alternative to DAC. This is a review of 53 consecutive PD patients between 2021 and 2022. Albumin, C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR), DAC, white blood cell count, and procalcitonin values were compared by CR-POPF status. The discriminatory abilities of CAR, CRP, and DAC for CR-POPF were compared using receiver operating characteristic (ROC) curves. Six of 51 included patients developed a CR-POPF. Receiver operating characteristic curve analysis produced an area under the curve of .977 for POD 1 DAC (cut-off 5131.0 IU/L, sensitivity 100%, specificity 95.5%), .858 for POD 1 CRP (cut-off 52.5mg/L, sensitivity 100%, specificity 72.7%), and 1.000 for POD 3 CAR (cut-off 99.2, sensitivity and specificity 100%). POD 3 CAR produced a positive and negative predictive value of 100%. The CAR and CRP provide early and accurate identification of patients with post-PD CR-POPFs. These markers offer a method of safe CR-POPF detection, when the gold standard DAC is unavailable, ultimately allowing for early intervention and patient rescue.

Non-Surgical Interventions for the Prevention of Clinically Relevant Postoperative Pancreatic Fistula-A Narrative Review.

Clinically relevant postoperative pancreatic fistula (CR-POPF) is the leading cause of morbidity and mortality after pancreatic surgery. Post-pancreatectomy acute pancreatitis (PPAP) has been increasingly understood as a precursor and exacerbator of CR-POPF. No longer believed to be the consequence of surgical technique, the solution to preventing CR-POPF may lie instead in non-surgical, mainly pharmacological interventions. Five databases were searched, identifying eight pharmacological preventative strategies, including neoadjuvant therapy, somatostatin and its analogues, antibiotics, analgesia, corticosteroids, protease inhibitors, miscellaneous interventions with few reports, and combination strategies. Two further non-surgical interventions studied were nutrition and fluids. New potential interventions were also identified from related surgical and experimental contexts. Given the varied efficacy reported for these interventions, numerous opportunities for clarifying this heterogeneity remain. By reducing CR-POPF, patients may avoid morbid sequelae, experience shorter hospital stays, and ensure timely delivery of adjuvant therapy, overall aiding survival where prognosis, particularly in pancreatic cancer patients, is poor.

Post-pancreatectomy acute pancreatitis after pancreatoduodenectomy: Analysis of a clinically-relevant complication in a single-center retrospective study

Background/Objectives: This study aimed to evaluate the frequency, clinical impact, and risk factors of post-pancreatectomy acute pancreatitis (PPAP) after pancreatoduodenectomy (PD) according to the definition proposed by the International Study Group for Pancreatic Surgery (ISGPS). Methodspatients undergoing PD between 2010 and 2021 were retrospectively analyzed. PPAP was defined according to the ISGPS criteria, including elevated serum amylase for 48 h and concurring pancreatitis alterations on a CT scan. Results272 patients were finally included in the study. PPAP occurred in 40 (14.7 %) patients, and it was significantly related to higher rates of clinically-relevant postoperative pancreatic fistula (CR-POPF) (p < 0.001), post-pancreatectomy hemorrhage (PPH) (p < 0.001) and major complications (Clavien-Dindo ≥ 3a) (p < 0.001). Moreover, PPAP in the absence of CR-POPF (n = 18) was significantly related to longer hospital stay (p < 0.001), PPH (p < 0.001), major complications (Clavien-Dindo≥ 3a, p = 0.001) and higher intensive care unit costs (p = 0.029) compared to patients not developing PPAP. In the univariable and multivariable analysis, the duct size (p = 0.004) and high-risk pathologies (p = 0.004) but not intraoperative bleeding (p = 0.066) represented independent risk factors for PPAP. In the same analysis, patients receiving a bridging therapy with low molecular-weight heparin showed significantly lower rates of PPAP (p = 0.045). ConclusionsPPAP represents a relevant complication after PD. Its risk factors are similar to those for CR-POPF, while anticoagulants could represent a possible prevention strategy.

Peri-firing compression in prevention of pancreatic fistula after distal pancreatectomy: A systematic review and a cohort study

Background/Aims: Clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP) occurs in 20%–40% of patients and remains a leading cause of morbidity and increased healthcare cost in this patient group. Recently, several studies suggested decreased risk of CR-POPF with the use of peri-firing compression (PFC) technique. The aim of this report was to conduct a systematic review to get an overview of the current knowledge on the use of PFC in DP. In addition, our experience with PFC was presented. Methods: The systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Also, 19 patients undergoing DP with the use of PFC at Oslo University Hospital were studied. The primary endpoint was incidence of CR-POPF. Results: Seven articles reporting a total of 771 patients were ultimately included in the systematic review. Only two of these were case–control studies examining outcomes in patients with and without PFC, while the rest were case series. These were heterogeneous in terms of staplers used, cartridge selection policy, and PFC technique. Both case–control studies reported significantly reduced CR- POPF incidence with PFC. Eight (21%) of our patients developed CR-POPF after DP with PFC. Only one patient developed CR-POPF among those with pancreatic transection site thickness ⩽1.5 cm. Conclusion: Evidence on potential benefits of PFC in DP is limited in quantity and quality. Our findings suggest that the use of PFC does not lead to reduction in the incidence of CR-POPF. Yet, there might be a benefit from PFC when dealing with a thin pancreas.

Machine Learning Based Prediction of Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy.

To develop a novel machine learning (ML) model to predict clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). Accurate prognostication of CR-POPF may allow for risk stratification and adaptive treatment strategies for potential PD candidates. However, antecedent models, such as the modified Fistula Risk Score (mFRS), are limited by poor discrimination and calibration. All records entailing PD within the 2014-2018 ACS NSQIP were identified. Additionally, patients undergoing PD at our institution between 2013 and 2021 were queried from our local data repository. An eXtreme Gradient Boosting (XGBoost) model was developed to estimate the risk of CR-POPF using data from the ACS NSQIP and evaluated using institutional data. Model discrimination was estimated using the area under the receiver operating characteristic (AUROC) and precision recall curve (AUPRC). Overall, 12,281 and 445 patients undergoing PD were identified within the 2014-2018 ACS NSQIP and our institutional registry, respectively. Application of the XGBoost and mFRS scores to the internal validation dataset revealed that the former model had significantly greater AUROC (0.72 vs. 0.68, P<0.001) and AUPRC (0.22 vs. 0.18, P<0.001). Within the external validation dataset, the XGBoost model remained superior to the mFRS with an AUROC of 0.79 (95% CI 0.74-0.84) versus 0.75 (95% CI 0.70-0.80, P<0.001). In addition, AUPRC was higher for the XGBoost model, compared to the mFRS. Our novel ML model consistently outperformed the previously validated mFRS within internal and external validation cohorts, thereby demonstrating its generalizability and utility for enhancing prediction of CR-POPF.

Serum Creatinine and Amylase in Drain to Predict Pancreatic Fistula Risk after Pancreatoduodenectomy

Introduction: The identification of patients with low risk of clinically relevant postoperative pancreatic fistula (CR-POPF) and postoperative hemorrhage (PPH) can guide drain removal after pancreatoduodenectomy (PD). However, drain fluid amylase (DFA) ≤5,000 U/L on postoperative day (POD) 1 does not robustly predict the absence of CR-POPF. Methods: Consecutive patients undergoing PD at Sun Yat-sen University Cancer Center between July 2018 and October 2021 were analyzed. Recursive partitioning analysis was used to classify patients into groups with different risks of CR-POPF and PPH. Results: Among 288 consecutive patients included, 99 patients (34.38%) developed CR-POPF (86 grade B and 13 grade C). Patients with CR-POPF had increased levels of preoperative creatinine (CRE) and POD1 CRE. The combination of POD1 CRE (>104 μmol/L or not) and POD1 DFA (>5,000 U/L or not) stratified patients into subgroups with the maximum difference in CR-POPF risk. The CR-POPF rates were 17.82% (36/202) in group A (POD1 CRE ≤104 μmol/L and POD1 DFA ≤5,000 U/L), 53.33% (8/15) in group B (POD1 CRE >104 μmol/L and POD1 DFA ≤5,000 U/L), and 77.46% (55/71) in group C (POD1 DFA >5,000 U/L). The PPH rates were 1.98% (4/202), 20.00% (3/15), and 19.72% (14/71) in groups A, B, and C, respectively. Conclusion: Patients with POD1 DFA ≤5,000 U/L and POD1 CRE >104 μmol/L have a high risk of CR-POPF and may not benefit from early drain removal. Patients with POD1 DFA ≤5,000 U/L and POD1 CRE ≤104 μmol/L have low risk of CR-POPF and PPH.

A novel prediction model of pancreatic fistula after pancreaticoduodenectomy using only preoperative markers

BackgroundSince clinically relevant postoperative pancreatic fistula (CR-POPF) can cause intra-abdominal hemorrhage and abscesses, leading to surgery-related deaths after pancreaticoduodenectomy (PD), its preoperative prediction is important to develop strategies for surgical procedures and perioperative management. This study aimed to establish a novel prediction model for CR-POPF using preoperative markers.MethodsOn a training set of 180 patients who underwent PD at the Yamaguchi University Hospital, a combination of CR-POPF predictors were explored using the leave-one-out method with a unique discrete Bayes classifier. This predictive model was confirmed using a validation set of 366 patients who underwent PD at the Osaka University Hospital.ResultsIn the training set, CR-POPF occurred in 60 (33%) of 180 patients and 130 (36%) of 366 patients in the validation set using selected markers. In patients with pancreatic ductal adenocarcinoma (PDAC), the main pancreatic duct (MPD) index showed the highest prognostic performance and could differentiate CR-POPF with 87% sensitivity and 81% specificity among 84 patients in the training set. In the validation set, the sensitivity and specificity of the MPD index-based model for 130 PDAC samples were 93% and 87%, respectively. In patients with non-PDAC, the MPD index/body mass index (BMI) combination showed the highest prognostic performance and could differentiate CR-POPF with 84% sensitivity and 57% specificity among 96 patients in the training set. In the validation set, the sensitivity and specificity of the MPD index/BMI-based model for 236 non-PDAC samples were 85% and 53%, respectively.ConclusionWe developed a novel prediction model for pancreatic fistulas after PD using only preoperative markers. The MPD index and MPD index/BMI combination will be useful for CR-POPF assessment in PDAC and non-PDAC samples, respectively.

Application of an innovative pancreaticojejunostomy technique with a modified set of perioperative management in pancreatoduodenectomy: a retrospective cohort study

How to reduce grade C postoperative pancreatic fistula (POPF) incidence after pancreaticoduodenectomy (PD) is the pursuit of pancreatic surgeons. This study introduced an innovative pancreaticojejunostomy (PJ) technique with a complete set of perioperative management. All 144 patients in this single-center retrospective cohort study underwent the same PJ technique and perioperative management. The primary endpoint was grade C POPF incidence. The secondary endpoints were grade B POPF rate, drain fluid amylase level, complications, hospital stay duration, and mortality. Risk factors for clinically-relevant POPF (CR-POPF) were assessed by logistic regression analysis. No patient (0.0%) experienced grade C POPF, while 44 (30.6%) developed grade B. No in-hospital death was recorded. Multivariate analysis found relatively high body mass index, laparoscopic surgery, and soft or moderate pancreatic texture independent risk factors for CR-POPF. Our novel PJ anastomosis with modified perioperative management helped avoid grade C POPF. However, grade B POPF incidence was relatively high to some extent because of the enhanced management itself.